Verhoef P, Meleady R, Daly L E, Graham I M, Robinson K, Boers G H
Division of Human Nutrition and Epidemiology, Wageningen Centre for Food Sciences and Wageningen University, Wageningen, The Netherlands.
Eur Heart J. 1999 Sep;20(17):1234-44. doi: 10.1053/euhj.1999.1522.
Elevated plasma total homocysteine (tHcy) is a known risk factor for vascular disease. Gender, age, and circulating levels of folate, vitamins B(6)and B(12)affect tHcy levels. Objectives To study associations of gender and age with levels of plasma tHcy, and to examine the relationships of tHcy and circulating levels of folate, vitamins B(6)and B(12)with risk of vascular disease in men and women (pre- and post-menopausal).
In a multicentre case-control study in Europe, 750 patients (544 men, 206 women) with documented vascular disease of the coronary, cerebral, or peripheral vessels and 800 control subjects (570 men, 230 women) were enrolled. Plasma tHcy levels (fasting and after methionine loading) and circulating levels of the vitamins were measured. Adjustment for age and centre was carried out for all statistical analyses, with additional adjustment for serum creatinine and vitamins for the tHcy comparisons between the sexes and between cases and controls. Risk analyses included adjustment for creatinine and traditional risk factors. Relationships between age, gender and tHcy were studied among control subjects only.
Fasting tHcy levels were lower in women than in men. Levels of tHcy showed a positive association with age, for both sexes. In the post-menopausal age category, female post-methionine load tHcy levels surpassed levels of men. Elevation of tHcy (defined as >80th percentile of controls) appeared to be at least as strong a risk factor for vascular disease in women as in men, even before the menopause. For post-methionine load tHcy, there was a 40% stronger association with vascular disease in women than in men. In both sexes, but especially in pre-menopausal women, low circulating levels of vitamin B(6)conferred a two- to threefold increased risk of vascular disease, independent of tHcy. In men, but not in women, low (defined as <20th percentile of controls) circulating folate levels were associated with a 50% increased risk of vascular disease.
Elevation of tHcy appears to be at least as strong a risk for vascular disease in women as men, even before the menopause. Our data indicate that associations of the various tHcy measurements (and the vitamins that determine them), with risks of vascular disease may differ between the sexes. The tHcy-independent relationship of vitamin B(6)with vascular disease indicates that it will be advisable to test the effects of vitamin B(6)in clinical trials.
血浆总同型半胱氨酸（tHcy）升高是已知的血管疾病危险因素。性别、年龄以及叶酸、维生素B6和B12的循环水平会影响tHcy水平。目的：研究性别和年龄与血浆tHcy水平的关联，并探讨tHcy以及叶酸、维生素B6和B12的循环水平与男性和女性（绝经前和绝经后）血管疾病风险的关系。
在欧洲一项多中心病例对照研究中，纳入了750例有冠状动脉、脑血管或外周血管疾病记录的患者（544例男性，206例女性）和800例对照者（570例男性，230例女性）。测量了血浆tHcy水平（空腹及蛋氨酸负荷后）和维生素的循环水平。所有统计分析均对年龄和中心进行了校正，在比较性别之间以及病例与对照之间的tHcy时，还对血清肌酐和维生素进行了额外校正。风险分析包括对肌酐和传统风险因素的校正。仅在对照者中研究年龄、性别与tHcy之间的关系。
女性空腹tHcy水平低于男性。tHcy水平在两性中均与年龄呈正相关。在绝经后年龄组中，女性蛋氨酸负荷后tHcy水平超过男性。tHcy升高（定义为高于对照者第80百分位数）似乎是女性血管疾病的危险因素，其强度至少与男性相当，甚至在绝经前也是如此。对于蛋氨酸负荷后tHcy，女性与血管疾病的关联比男性强40%。在两性中，尤其是绝经前女性，维生素B6循环水平低会使血管疾病风险增加2至3倍，且独立于tHcy。在男性中，而非女性中，循环叶酸水平低（定义为低于对照者第20百分位数）与血管疾病风险增加50%相关。
tHcy升高似乎是女性血管疾病的危险因素，其强度至少与男性相当，甚至在绝经前也是如此。我们的数据表明，各种tHcy测量值（以及决定它们的维生素）与血管疾病风险的关联在两性之间可能有所不同。维生素B6与血管疾病的tHcy独立关系表明，在临床试验中测试维生素B6的效果是可取的。
